tbuckley/cabot-search huggingface dataset:
Geometric Mismatch Promotes Anatomic Repair in Periorbital Bony Defects in Skeletally Mature Yucatan Minipigs
Authors: Srujan Singh, Yuxiao Zhou, Ashley L. Farris, Emma C. Whitehead, Ethan L. Nyberg, Aine N. O'Sullivan, Nicholas Y. Zhang, Alexandra N. Rindone, Chukwuebuka C. Achebe, Wojciech Zbijewski, Will Grundy, David Garlick, Nicolette D. Jackson, Dara Kraitchman, Jessica M. Izzi, Joseph Lopez, Michael P. Grant, Warren L. Grayson
Journal: Advanced Healthcare Materials (2023)

Porous tissue-engineered 3D-printed scaffolds are a compelling alternative to autografts for the treatment of large periorbital bone defects. Matching the defect-specific geometry has long been considered an optimal strategy to restore pre-injury anatomy. However, studies in large animal models have revealed that biomaterial-induced bone formation largely occurs around the scaffold periphery. Such ectopic bone formation in the periorbital region can affect vision and cause disfigurement. To enhance anatomic reconstruction, geometric mismatches are introduced in the scaffolds used to treat full thickness zygomatic defects created bilaterally in adult Yucatan minipigs. 3D-printed, anatomically-mirrored scaffolds are used in combination with autologous stromal vascular fraction of cells (SVF) for treatment. An advanced image-registration workflow is developed to quantify the post-surgical geometric mismatch and correlate it with the spatial pattern of the regenerating bone. Osteoconductive bone growth on the dorsal and ventral aspect of the defect enhances scaffold integration with the native bone while medio-lateral bone growth leads to failure of the scaffolds to integrate. A strong positive correlation is found between geometric mismatch and orthotopic bone deposition at the defect site. The data suggest that strategic mismatch >20% could improve bone scaffold design to promote enhanced regeneration, osseointegration, and long-term scaffold survivability.
Gut microbiota diversity before allogeneic hematopoietic stem cell transplantation as a predictor of mortality in children
Authors: Riccardo Masetti, Davide Leardini, Edoardo Muratore, Marco Fabbrini, Federica D’Amico, Daniele Zama, Francesco Baccelli, Francesca Gottardi, Tamara Belotti, Marek Ussowicz, Jowita Fraczkiewicz, Simone Cesaro, Marco Zecca, Pietro Merli, Marco Candela, Andrea Pession, Franco Locatelli, Arcangelo Prete, Patrizia Brigidi, Silvia Turroni
Journal: Blood (2023)

Abstract The correlation existing between gut microbiota diversity and survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has so far been studied in adults. Pediatric studies question whether this association applies to children as well. Stool samples from a multicenter cohort of 90 pediatric allo-HSCT recipients were analyzed using 16S ribosomal RNA amplicon sequencing to profile the gut microbiota and estimate diversity with the Shannon index. A global-to-local networking approach was used to characterize the ecological structure of the gut microbiota. Patients were stratified into higher- and lower-diversity groups at 2 time points: before transplantation and at neutrophil engraftment. The higher-diversity group before transplantation exhibited a higher probability of overall survival (88.9% ± 5.7% standard error [SE] vs 62.7% ± 8.2% SE; P = .011) and lower incidence of grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD). No significant difference in relapse-free survival was observed between the 2 groups (80.0% ± 6.0% SE vs 55.4% ± 10.8% SE; P = .091). The higher-diversity group was characterized by higher relative abundances of potentially health-related microbial families, such as Ruminococcaceae and Oscillospiraceae. In contrast, the lower-diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae. Network analysis detected short-chain fatty acid producers, such as Blautia, Faecalibacterium, Roseburia, and Bacteroides, as keystones in the higher-diversity group. Enterococcus, Escherichia-Shigella, and Enterobacter were instead the keystones detected in the lower-diversity group. These results indicate that gut microbiota diversity and composition before transplantation correlate with survival and with the likelihood of developing aGVHD.
Melanoma-derived mediators can foster the premetastatic niche: crossroad to lymphatic metastasis
Authors: Shankar Suman, Svetomir N. Markovic
Journal: Trends in Immunology (2023)

The natural history of advanced malignant melanoma demonstrates that, in most cases, widespread tumor dissemination is preceded by regional metastases involving tumor-draining lymph nodes [sentinel lymph nodes (SLNs)]. Under physiological conditions, LNs play a central role in immunosurveillance to non-self-antigens to which they are exposed via afferent lymph. The dysfunctional immunity in SLNs is mediated by tumor secretory factors that allow the survival of metastatic melanoma cells within the LN by creating a premetastatic niche (PMN). Recent studies outline the altered microenvironment of LNs shaped by melanoma mediators. Here, we discuss tumor secretory factors involved in subverting tumor immunity and remodeling LNs and highlight emerging therapeutic strategies to reinvigorate antitumoral immunity in SLNs.
Maast: genotyping thousands of microbial strains efficiently
Authors: Zhou Jason Shi, Stephen Nayfach, Katherine S. Pollard
Journal: Genome biology (2023)

Abstract Existing single nucleotide polymorphism (SNP) genotyping algorithms do not scale for species with thousands of sequenced strains, nor do they account for conspecific redundancy. Here we present a bioinformatics tool, Maast, which empowers population genetic meta-analysis of microbes at an unrivaled scale. Maast implements a novel algorithm to heuristically identify a minimal set of diverse conspecific genomes, then constructs a reliable SNP panel for each species, and enables rapid and accurate genotyping using a hybrid of whole-genome alignment and k-mer exact matching. We demonstrate Maast’s utility by genotyping thousands of Helicobacter pylori strains and tracking SARS-CoV-2 diversification.
Can Pulmonary Arterial Compliance Be a Prognostic Marker for Pulmonary Hypertension?
Authors: Yanjuan Wu, Xiaofen Su, Jingcun Wang, Haojie Zhang, Xiangxia Zeng, Sun Zhang, Nuofu Zhang, Kang Wu
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Can Pulmonary Arterial Compliance Be a Prognostic Marker for Pulmonary Hypertension?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
High–Temporal/High–Spatial Resolution Breast Magnetic Resonance Imaging Improves Diagnostic Accuracy Compared With Standard Breast Magnetic Resonance Imaging in Patients With High Background Parenchymal Enhancement
Authors: Sarah Eskreis-Winkler, Janice S. Sung, Linden Dixon, Natasha Monga, Ragni Jindal, Amber Simmons, Sunitha Thakur, Varadan Sevilimedu, Elizabeth Sutton, Christopher Comstock, Kimberly Feigin, Katja Pinker
Journal: Journal of Clinical Oncology (2023)

To compare breast magnetic resonance imaging (MRI) diagnostic performance using a standard high-spatial resolution protocol versus a simultaneous high-temporal/high-spatial resolution (HTHS) protocol in women with high levels of background parenchymal enhancement (BPE).
Acceptor engineering-facilitated versatile AIEgen for mitochondria-targeted multimodal imaging-guided cancer photoimmunotherapy
Authors: Zhe Sun, Haifei Wen, Zhijun Zhang, Weilin Xu, Mengni Bao, Han Mo, Xiumeng Hua, Jianlou Niu, Jiangping Song, Miaomiao Kang, Dong Wang, Ben Zhong Tang
Journal: Biomaterials (2023)
Cardiac sequelae in athletes following COVID-19 vaccination: evidence and misinformation
Authors: Joelle Julius Nicolaas Daems, Juliette C van Hattum, Sjoerd M Verwijs, Nick R Bijsterveld, Maarten Groenink, Arthur A M Wilde, Yigal M Pinto, Harald T Jorstad
Journal: British Journal of Sports Medicine (2023)

The recognition of myocarditis as a rare side effect of SARS-CoV-2 mRNA vaccination has sparked a global debate on vaccine safety, especially in the realm of sports. The main proposed mechanisms in the pathogenesis of COVID-19 mRNA vaccination-associated myocarditis (C-VAM) are based on the activation of the innate- and adaptive immune system against a susceptible immune-genetic background, including the recognition of mRNA as an antigen by the immune system, molecular mimicry between SARS-CoV-2 spike glycoprotein and cardiac tissue antigens and inflammatory sex-hormone signalling. The relatively younger age of the athlete population hypothetically constellates an increased risk of C-VAM. A subgroup analysis in individuals under 40 years revealed a low incidence of myocarditis following COVID-19 mRNA vaccination when compared to positive SARS-CoV-2 tests. No confirmed cases of athletes experiencing cardiac complications after mRNA vaccination have been reported. Most athletes only reported mild side effects after COVID-19 vaccination. A small but statistically significant decrease in maximal oxygen consumption in recreational athletes occurred after BNT162b2 mRNA booster vaccine administration. The clinical relevance and temporality of which remain to be determined. Many speculative social media reports attribute sudden cardiac arrest/death (SCA/D) in athletes to mRNA vaccination. Large media outlets have thoroughly debunked these claims. There is currently no evidence to support the claim that COVID-19 mRNA vaccination increases the risk of myocardial sequelae or SCA/D in athletes. However, specific vaccine regimen selection and timing may be appropriate to prevent detrimental performance effects.
P655: LIMITATIONS OF USING CD26+ LEUKEMIA STEM CELL QUANTITATION IN CML PATIENTS TO ASSESS RESIDUAL LEUKEMIA CLONE
Authors: Nikolay Kapranov, Yulia Davydova, Kseniya Nikiforova, Irina Galtseva, Oleg Shukhov, Margarita Gurianova, Ekaterina Chelysheva, Anna Turkina
Journal: HemaSphere (2023)

Background: Recent findings show that there is a population of stem cell (SC) highly specific for patients with chronic myeloid leukemia (CML). These cells are “immature” CD34+CD38low/neg SC and show expression of CD26, which is atypical for normal SC. These cells supposed to be CML leukemic stem cells (LSC). The presence of residual LSCs detected by flow cytometry (FC) in the peripheral blood of CML patients with a deep molecular response (DMR) has been demonstrated by several recent studies. The influence of residual LSCs on treatment-free remission and the reproducibility of methods for their determination require further study. Aims: To determine the representation of residual LSCs in patients with DMR and their significance for maintaining remission after stopping therapy. Methods: We analyzed 185 samples from 125 patients in chronic phase CML (133 blood and 52 bone marrow samples). The analysis included patients with DMR (at least MR4) and a control group of patients with de novo CML. The group of patients with DMR consisted of patients who were scheduled to discontinue therapy (n=43, blood samples n=52, bone marrow samples n=17) and patients who successfully discontinued TKIs (n=24, blood samples n=24). The control group consisted of 58 de novo CML patients (blood samples n=57, bone marrow samples n=35). The median level of BCR-ABL in the group of patients in the onset of CML was 81.1% (IQR 66.9-91.5). Detection of CML LSCs was performed by FC on BC CytoFlex flow cytometer. The analysis included 4 antigens (CD45, CD34, CD38 and CD26) and viability dye. At least 106 viable cells per sample were analysed (median 1.7×106). Descriptive statistics methods were used in the analysis. Comparative analysis of LSCs concentration was performed using the Man-Whitney test. Results: In the control group of patients with de novo CML, the median concentration of LSC cells in the bone marrow was 50.76 per µl (IQR 16.37-116.96) and 26.29 per µL (IQR 4.67-83.93) in blood samples (p=0.09). In one patient, at the onset of CML, CD26+ LSCs was not detected. None of patients with DMR, both on treatment and after discontinuation of TKI therapy, showed CD26 + LSCs in the blood or bone marrow samples (fig. 1). Summary/Conclusion: The CD26+LSCs compartment is detected in the blood and bone marrow in 98% (57/58) of patients at the onset of CML and is absent in patients with DMR both to TKI therapy and after discontinuation of therapy. This method is neither an alternative nor an adjunct to quantitative real-time PCR to select patients for stopping TKI therapy. The main cause in controversial results between different research groups is a lack of standardization in FC of CML LSC which includes gating strategy, reagents selection, protocols and flow cytometers on which analysis is performed. Keywords: Chronic myeloid leukemia, Leukemic stem cell
A Bone Targeting Nanoparticle Loaded OGP to Restore Bone Homeostasis for Osteoporosis Therapy
Authors: Shiqing Ma, Shendan Xu, Minting Li, Yaqi Du, Guangjie Tian, Jiayin Deng, Wenyi Zhang, Pengfei Wei, Bo Zhao, Xuesong Zhang, Zihao Liu, Yonglan Wang
Journal: Advanced Healthcare Materials (2023)

Restoring bone homeostasis is the key to the treatment of osteoporosis. How to increase osteogenic ability or inhibit osteoclast activity has always been a topic of great concern. In recent years, short peptides with biological activity have received great attention in bone repair. However, the application of short peptides is still limited due to the lack of a stable and targeted delivery system. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles modified by alendronate (AL) to transport osteogenic peptides (OGP) (AL-PLGA@P NPs) are designed. Benefiting from the high affinity of AL for hydroxyapatite, AL-PLGA@P NPs have the ability to target bone. In this delivery system, OGP that promotes osteogenesis synergizes with AL, which inhibits osteoclasts, to regulate bone homeostasis, which gives them more advantages in the treatment of osteoporosis. The data shows that nanoparticles can selectively deliver peptides to the bone surface without systemic toxicity. Moreover, nanoparticles can upregulate osteogenesis-related factors (ALP, Runx-2, and BMP2) and downregulate osteoclast-related factors (TRAP and CTSK) in vitro. With AL-PLGA@P NPs, bone microarchitecture and bone mass are improved in ovariectomized osteoporosis rats. Therefore, this study proposes a novel osteoporosis-based drug system that effectively improves bone density.
Clinical and cost-effectiveness of nurse-delivered sleep restriction therapy for insomnia in primary care (HABIT): a pragmatic, superiority, open-label, randomised controlled trial
Authors: Simon D Kyle, A Niroshan Siriwardena, Colin A Espie, Yaling Yang, Stavros Petrou, Emma Ogburn, Nargis Begum, Leonie F Maurer, Barbara Robinson, Caroline Gardner, Victoria Lee, Stephanie Armstrong, Julie Pattinson, Sam Mort, Eleanor Temple, Victoria Harris, Ly-Mee Yu, Peter Bower, Paul Aveyard
Journal: The Lancet (2023)

Insomnia is prevalent and distressing but access to the first-line treatment, cognitive behavioural therapy (CBT), is extremely limited. We aimed to assess the clinical and cost-effectiveness of sleep restriction therapy, a key component of CBT, which has the potential to be widely implemented.We did a pragmatic, superiority, open-label, randomised controlled trial of sleep restriction therapy versus sleep hygiene. Adults with insomnia disorder were recruited from 35 general practices across England and randomly assigned (1:1) using a web-based randomisation programme to either four sessions of nurse-delivered sleep restriction therapy plus a sleep hygiene booklet or a sleep hygiene booklet only. There was no restriction on usual care for either group. Outcomes were assessed at 3 months, 6 months, and 12 months. The primary endpoint was self-reported insomnia severity at 6 months measured with the insomnia severity index (ISI). The primary analysis included participants according to their allocated group and who contributed at least one outcome measurement. Cost-effectiveness was evaluated from the UK National Health Service and personal social services perspective and expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. The trial was prospectively registered (ISRCTN42499563).Between Aug 29, 2018, and March 23, 2020 we randomly assigned 642 participants to sleep restriction therapy (n=321) or sleep hygiene (n=321). Mean age was 55·4 years (range 19-88), with 489 (76·2%) participants being female and 153 (23·8%) being male. 580 (90·3%) participants provided data for at least one outcome measurement. At 6 months, mean ISI score was 10·9 (SD 5·5) for sleep restriction therapy and 13·9 (5·2) for sleep hygiene (adjusted mean difference -3·05, 95% CI -3·83 to -2·28; p<0·0001; Cohen's d -0·74), indicating that participants in the sleep restriction therapy group reported lower insomnia severity than the sleep hygiene group. The incremental cost per QALY gained was £2076, giving a 95·3% probability that treatment was cost-effective at a cost-effectiveness threshold of £20 000. Eight participants in each group had serious adverse events, none of which were judged to be related to intervention.Brief nurse-delivered sleep restriction therapy in primary care reduces insomnia symptoms, is likely to be cost-effective, and has the potential to be widely implemented as a first-line treatment for insomnia disorder.The National Institute for Health and Care Research Health Technology Assessment Programme.
Hear and Now: Ongoing Clinical Trials to Prevent Drug-Induced Hearing Loss
Authors: John Lee, Katharine Fernandez, Lisa L. Cunningham
Journal: The Annual Review of Pharmacology and Toxicology (2023)

Each year over half a million people experience permanent hearing loss caused by treatment with therapeutic drugs with ototoxic side effects. There is a major unmet clinical need for therapies that protect against this hearing loss without reducing the therapeutic efficacy of these lifesaving drugs. At least 17 clinical trials evaluating 10 therapeutics are currently underway for therapies aimed at preventing aminoglycoside- and/or cisplatin-induced ototoxicity. This review describes the preclinical and clinical development of each of these approaches, provides updates on the status of ongoing trials, and highlights the importance of appropriate outcome measures in trial design and the value of reporting criteria in the dissemination of results.
Evolution of Human Brain Left–Right Asymmetry: Old Genes with New Functions
Authors: Jianguo Wang, Sidi Ma, Peijie Yu, Xionglei He
Journal: Molecular Biology and Evolution (2023)

Abstract The human brain is generally anatomically symmetrical, boasting mirror-like brain regions in the left and right hemispheres. Despite this symmetry, fine-scale structural asymmetries are prevalent and are believed to be responsible for distinct functional divisions within the brain. Prior studies propose that these asymmetric structures are predominantly primate specific or even unique to humans, suggesting that the genes contributing to the structural asymmetry of the human brain might have evolved recently. In our study, we identified approximately 1,500 traits associated with human brain asymmetry by collecting paired brain magnetic resonance imaging features from the UK Biobank. Each trait is measured in a specific region of one hemisphere and mirrored in the corresponding region of the other hemisphere. Conducting genome-wide association studies on these traits, we identified over 1,000 quantitative trait loci. Around these index single nucleotide polymorphisms, we found approximately 200 genes that are enriched in brain-related Gene Ontology terms and are predominantly upregulated in brain tissues. Interestingly, most of these genes are evolutionarily old, originating just prior to the emergence of Bilateria (bilaterally symmetrical animals) and Euteleostomi (bony vertebrates with a brain), at a significantly higher ratio than expected. Further analyses of these genes reveal a brain-specific upregulation in humans relative to other mammalian species. This suggests that the structural asymmetry of the human brain has been shaped by evolutionarily ancient genes that have assumed new functions over time.
Pembrolizumab in Patients With Tumors With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry Study
Authors: Herbert L. Duvivier, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Eugene R. Ahn, Tareq Al Baghdadi, Ajjai S. Alva, Stephanie A. Dublis, Timothy L. Cannon, Carmen J. Calfa, Rui Li, Deepti Behl, Vi K. Chiu, Philip J. Gold, Alissa S. Marr, Kathryn F. Mileham, Steven Francis Powell, Jordi Rodon, Ramya Thota, Gina N. Grantham, Abigail Gregory, Dominique C. Hinshaw, Susan Halabi, Richard L. Schilsky
Journal: Journal of Clinical Oncology (2023)

The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a pragmatic basket trial evaluating antitumor activity of approved targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from cohorts of patients with high tumor mutational burden (HTMB, defined as ≥9 mutations per megabase) with advanced colorectal cancer (CRC) and other advanced cancers treated with pembrolizumab are reported.Eligible patients were 18 years and older with measurable tumors and a lack of standard treatment options, an Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. The primary end point was disease control (DC), defined as complete or partial response or stable disease (SD) of at least 16-weeks duration. For the CRC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. Low accruing histology-specific cohorts were collapsed into one histology-pooled (HP) cohort. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included objective response (OR), safety, progression-free survival, overall survival, duration of response, and duration of SD.Seventy-seven patients with HTMB with CRC (n = 28) or advanced cancers (n = 49) were treated with pembrolizumab. For the CRC cohort, the DC rate was 31% (P = .04) and the OR rate was 11%. For the HP cohort, the DC rate was 45% (one-sided 90% CI, 35 to 100) and the OR rate was 26%. The null hypothesis of a 15% DC rate was rejected for both cohorts. Twelve of 77 patients experienced treatment-related grade 3 adverse events (AEs) or serious AEs, including two deaths.Pembrolizumab demonstrated antitumor activity in pretreated patients with advanced cancers and HTMB.